{"doi":"10.1002/jbmr.426","title":"Histone deacetylase inhibitor MS-275 stimulates bone formation in part by enhancing Dhx36-mediated TNAP transcription","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Histone deacetylases (HDACs) deacetylate both histones and nonhistone proteins and play a key role in the regulation of physiologic and aberrant gene expression. Inhibition of HDACs has emerged as a promising therapeutic target for cancer and neurologic diseases. In this study we investigated the osteogenic effect and mechanism of action of MS-275, a class I HDAC inhibitor with preference for HDAC1. Both local and systemic administration of MS-275 stimulated bone regeneration in animal models. MS-275 stimulated mRNA expression and activity of the early osteogenic marker tissue-nonspecific alkaline phosphatase (TNAP) in bone tissue and osteogenic cells. By using a series of TNAP promoter deletion constructs and a DNA affinity precipitation assay, we identified DExH-box helicase Dhx36 as a factor that binds to the MS-275 response element in the TNAP promoter. We also found that Dhx36 binding to the MS-275 response element is crucial for MS-275 induction of TNAP transcription. Dhx36 physically interacted with a subset of HDACs (HDAC1 and -4) whose protein levels were downregulated by MS-275, and forced expression of these HDACs blunted the stimulatory effects of MS-275 by a deacetylase activity–independent mechanism(s). Taken together, the results of our study show that MS-275 induces TNAP transcription by decreasing the interaction of HDAC1/4 with Dhx36, which can at least in part contribute to the bone anabolic effects of MS-275. © 2011 American Society for Bone and Mineral Research</jats:p>","journal":"Journal of Bone and Mineral Research","year":2011,"id":13669,"datarank":2.1819145362863965,"base_score":4.04305126783455,"endowment":4.04305126783455,"self_citation_contribution":0.6064576901751826,"citation_network_contribution":1.5754568461112137,"self_endowment_contribution":0.6064576901751826,"citer_contribution":1.5754568461112137,"corpus_percentile":null,"corpus_rank":null,"citation_count":56,"citer_count":46,"citers_with_citation_signal":44,"citers_with_endowment":44,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":111188,"name":"Jong-Ho Lee","orcid":null,"position":1,"is_corresponding":false},{"id":111189,"name":"Suk-Chul Bae","orcid":null,"position":2,"is_corresponding":false},{"id":111190,"name":"Hyun-Mo Ryoo","orcid":null,"position":3,"is_corresponding":false},{"id":111191,"name":"Hong-Hee Kim","orcid":null,"position":4,"is_corresponding":false},{"id":111192,"name":"Hyunil Ha","orcid":null,"position":5,"is_corresponding":false},{"id":111193,"name":"Zang Hee Lee","orcid":"0000-0003-1466-357X","position":6,"is_corresponding":false},{"id":111187,"name":"Ha-Neui Kim","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.04305126783455,"endowment":4.04305126783455,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21590736","pmcid":null,"openalex_id":"https://openalex.org/W2056022631","authors":[],"funders":[],"total_grants":0,"fwci":1.3302,"citation_percentile":0.79551279,"influential_citations":1,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":4},{"year":2015,"count":6},{"year":2016,"count":5},{"year":2017,"count":1},{"year":2018,"count":3},{"year":2019,"count":2},{"year":2020,"count":4},{"year":2021,"count":9},{"year":2022,"count":5},{"year":2023,"count":5},{"year":2024,"count":5},{"year":2025,"count":1}],"oa_status":"closed","license":"https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjbmr.426","host_type":"publisher"},{"url":"https://academic.oup.com/jbmr/article-pdf/26/9/2161/56558378/426_ftp.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1002/jbmr.426","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21590736","host_type":"repository"},{"url":"http://hdl.handle.net/10371/80874","host_type":"repository"}],"fields_of_study":["Histone Deacetylase Inhibitors Research","Biochemical and Molecular Research","Signaling Pathways in Disease","Biology","Medicine","Alkaline Phosphatase","Animals","Base Sequence","Benzamides","Bone Regeneration","Cell Differentiation","Cell Line","DEAD-box RNA Helicases","Gene Knockdown Techniques","Histone Deacetylase Inhibitors","Histone Deacetylases","Humans","Isoenzymes","Male","Mice","Molecular Sequence Data","Osteogenesis","Protein Binding","Pyridines","Rats","Rats, Sprague-Dawley","Response Elements","Transcription, Genetic"],"mesh_terms":["Alkaline Phosphatase","Animals","Base Sequence","Benzamides","Bone Regeneration","Cell Differentiation","Cell Line","Histone Deacetylases","Humans","Isoenzymes","Male","Molecular Sequence Data","Osteogenesis","Protein Binding","Pyridines","Transcription, Genetic","Rats, Sprague-Dawley","Response Elements","Mice","Rats","DEAD-box RNA Helicases","Gene Knockdown Techniques","Histone Deacetylase Inhibitors"],"keywords":["HDAC1","Histone deacetylase","Transcription factor","Chemistry","Histone","Transcription (linguistics)","Cell biology","Molecular biology","Cancer research","Biology","Biochemistry","DNA","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-05-31T09:05:02.523798Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}